Preparation of a pure autologous biodegradable fibrin matrix for tissue engineering
Parallel to the growing role of tissue engineering, the need for cell embedding materials, which allow cells to stabilise in a three-dimensional distribution, has increased. Although several substances have been tested, fibrin is thus far the only one that permits the clinical application of cultured tissue. To date, autologous fibrinogen has usually been polymerised with bovine thrombin, which can cause severe immunological side effects. The objective of this study was to explore the practicability of obtaining autologous thrombin from a single patient in an adequate concentration and amount. Fibrinogen was cryoprecipitated from 200 ml of freshly-frozen plasma. Thrombin was isolated from the supernatant through ion-exchange chromatography. The thrombin was first bound to Sephadex A-50 and then eluated using 2 ml of a salt buffer (2.0 M NaCl in 0.015 M trisodiumcitrate, pH 7.0). The activity of the thrombin (51 NIH x ml(-1) to 414 NIH x ml(-1) reached levels comparable to those in commercially available fibrin glues (4-500 NIH x ml(-1)). The study has shown that it is possible to obtain a sufficient amount of autologous thrombin from a single donor to create a fibrin matrix of high efficiency without the risk of immunological and infectious side effects.
Available from: Nicolas L'Heureux
- "As an alternative to collagen scaffolds, a number of groups have also researched the use of cell-impregnated fibrin gels to create vascular grafts. While most studies have been performed with isolated/processed components , a possible advantage of using fibrin is that fibrinogen and thrombin, the precursors to fibrin gel formation, can be readily obtained from a patient's own blood [Haisch et al., 2000]. Like collagen gel-based grafts, constructs created from fibrin-gels have a typically low mechanical strength. "
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ABSTRACT: Dacron® (polyethylene terephthalate) and Goretex® (expanded polytetrafluoroethylene) vascular grafts have been very successful in replacing obstructed blood vessels of large and medium diameters. However, as diameters decrease below 6 mm, these grafts are clearly outperformed by transposed autologous veins and, particularly, arteries. With approximately 8 million individuals with peripheral arterial disease, over 500,000 patients diagnosed with end-stage renal disease, and over 250,000 patients per year undergoing coronary bypass in the USA alone, there is a critical clinical need for a functional small-diameter conduit [Lloyd-Jones et al., Circulation 2010;121:e46-e215]. Over the last decade, we have witnessed a dramatic paradigm shift in cardiovascular tissue engineering that has driven the field away from biomaterial-focused approaches and towards more biology-driven strategies. In this article, we review the preclinical and clinical efforts in the quest for a tissue-engineered blood vessel that is free of permanent synthetic scaffolds but has the mechanical strength to become a successful arterial graft. Special emphasis is given to the tissue engineering by self-assembly (TESA) approach, which has been the only one to reach clinical trials for applications under arterial pressure.
Available from: Dietmar W. Hutmacher
- "Based on this strategy the advantages of synthetic and natural polymers can be straightforwardly combined to provide a 3D cell arrangement mimicking the in vivo situation as closely as possible. Fibrin gel was selected as a model gel for the rabbit study because it is an FDAapproved material, has been used extensively in the clinical setting as a tissue adhesive  as well as a cell carrier in epidermal skin tissue engineering  and can also be obtained from a patients' own blood . Favourable healing processes could potentially be promoted because a multiple material matrix facilitates the entrapment of soluble or immobilized factors within the gel phase while providing high and homogenous seeding efficiency and efficacy within the polymer construct  . "
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ABSTRACT: Tissue engineering of an elastic cartilage graft that meets the criterion for both structural and functional integration into host tissue, as well as allowing for a clinically tolerable immune response, is a challenging endeavour. Conventional scaffold technologies have limitations in their ability to design and fabricate complex-shaped matrix architectures of structural and mechanical equivalence to elastic cartilage found in the body. We attempted to investigate the potential of conventionally isolated and passaged chondrocytes (2D environment) when seeded and cultured in combination with a biomimetic hydrogel in a mechanically stable and biomimetic composite matrix to form elastic cartilage within ectopic implantation sites. In vitro cultured scaffold/hydrogel/chondrocytes constructs showed islets of cartilage and mineralized tissue formation within the cell-seeded specimens in both pig and rabbit models. Specimens with no cells seeded showed only vascularized fibrous tissue ingrowth. These studies demonstrated the potential of such scaffold/hydrogel/cell constructs to support chondrogenesis in vivo. However, it also showed that even mechanically stable scaffolds do not allow regeneration of a large mass of structural and functional cartilage within a matrix architecture seeded with 2D passaged chondrocytes in combination with a cell biomimetic carrier. Hence, future experiments will be designed to evaluate an initial 3D culture of chondrocytes, effect on cell phenotype and their subsequent culture within biomimetic 3D scaffold/cell constructs.
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ABSTRACT: Stem cell therapy is a leading field of research worldwide given its promising potential for recovery or replacement of tissues
and organs, especially for the treatment of cardiovascular pathologies. However, despite this enormous experimental effort
and the reported positive results in different models, there is no conclusive demonstration of the mechanisms involved in
tissue regeneration associated to adult stem cell treatment. This represents one of the major limitations for the clinical
translation of stem cell therapy. A real regenerative medicine approach should consider the importance of the extracellular
matrix (ECM) and the strong biological signals that it can provide. Connective tissue atmosphere in which cells are embedded
exerts a number of actions affecting cells function and supporting their proliferation and differentiation. Polymeric electrospun
matrices are among the most promising ECM-mimetic biomaterials, because of their physical structure closely resembling the
fibrous proteins in native ECM. Moreover, electrospun materials can be easily functionalized with bioactive molecules providing
localized biochemical stimuli to cells seeded therein. The idea of taking advantage of both stem cells plasticity and biomaterials that actively guide
and provide the correct sequence of signals to allow ongoing lineage-specific differentiation is an attractive alternative
and may represent a promising answer to the treatment limitations of cardiovascular severe diseases.
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